TDP43

A total of 12 presentations including 6 original posters to showcase MTPA's latest ALS research JERSEY CITY, N.J., Oct. 17, 2024 /PRNewswire/ -- Mitsubishi Tanabe Pharma America, Inc. (MTPA) today announced that twelve presentations following expansive research in amyotrophic lateral sclerosis (ALS) will be shared as part of the Northeast Amyotrophic Lateral Sclerosis Consortium (NEALS) 2024 Annual Meeting, being held virtually October 21-24. "We are excited to present our latest data in ALS research, from preclinical studies to extensive real-world data on RADICAVA® (edaravone) at this year's meeting," said Gustavo A. Suarez Zambrano, M.D., Vice President of Medical Affairs, MTPA. "Our unwavering commitment to ALS research drives us to provide valuable insights to patients, healthcare practitioners and researchers alike, with the ultimate goal of providing treatment options to help improve the lives of those affected by this disease." RADICAVA ORS Results: A presentation will examine the impact of RADICAVA ORS on survival and function in ALS patients, using data from the Pooled Resource Open-Access ALS Clinical Trials (PRO-ACT) database. For this analysis, patients were propensity score-matched with participants from studies MT-1186 A01-A04. Additionally, multiple presentations will explore RADICAVA ORS through multi-center, phase 3b, double-blind, parallel group studies, including a comparison of daily dosing to the U.S. Food and Drug Administration (FDA)-approved on/off regimen, evaluated over 48 weeks (MT-1186-A02) and up to 96 weeks (MT-1186-A04). Safety data from the phase 3 open-label safety extension study (MT-1196-A03) and a post-marketing safety analysis will also be presented. Analysis of Long-term Function and Survival of Radicava ORS® (Oral Edaravone)-Treated Patients With Amyotrophic Lateral Sclerosis vs Propensity Score–Matched PRO-ACT Historical Controls (Stephen Apple, M.D.; MTPA) Poster Session: 4:00 p.m. - 6:00 p.m. ET, Wednesday, October 23 Phase 3b Study MT-1186-A02 to Investigate the Superiority of Daily Dosing vs the FDA-approved On/Off Regimen of Oral Edaravone in Patients with ALS (Alejandro Salah, M.D., Ph.D., MBA, MHA; MTPA) Poster Session: 4:00 p.m. - 6:00 p.m. ET, Wednesday, October 23 Phase 3b Study MT-1186-A04 Extension Study to Evaluate the Continued Efficacy and Safety of Radicava ORS® (Oral Edaravone) for up to an Additional 48-Weeks in Patients With Amyotrophic Lateral Sclerosis (Stephen Apple, M.D.; MTPA) Poster Session: 4:00 p.m. - 6:00 p.m. ET, Wednesday, October 23 Phase 3, Open-Label, Safety Extension Study of Oral Edaravone Administered Over 96 Weeks in Patients with ALS (MT-1186-A03) (Alejandro Salah, M.D., Ph.D., MBA, MHA; MTPA) Poster Session: 4:00 p.m. - 6:00 p.m. ET, Wednesday, October 23 Summary of the US Safety Data for Radicava ORS®: Findings From the Postmarketing Pharmacovigilance (Stephen Apple, M.D.; MTPA) Poster Session: 4:00 p.m. - 6:00 p.m. ET, Wednesday, October 23 Real World Data: Data will be presented from an evaluation of treatment patterns, clinical outcomes and survival rates of RADICAVA-treated individuals living with ALS from the ALS/Motor Neuron Disease (MND) Natural History Consortium (NHC) registry. Additionally, a preliminary analysis will examine the treatment combinations in people with ALS enrolled in the OPTUM claims database. Other presentations include two studies focused on point-of-care quality classifications and at-home telespirometry, evaluating erect and supine slow vital capacity in individuals with ALS, as well as an observational study, Track-ALS, assessing participant compliance and the usability of digital health technologies (DHTs) to remotely monitor ALS progression. Treatment Patterns and Survival Benefit of Edaravone–Treated People With Amyotrophic Lateral Sclerosis in the ALS/MND Natural History Consortium (Stephen Apple, M.D.; MTPA) Poster Session: 4:00 p.m. - 6:00 p.m. ET, Wednesday, October 23 Preliminary Analysis of Treatment Combinations in Patients With Amyotrophic Lateral Sclerosis Enrolled in an US-Based Administrative Claims Database (Malgorzata Ciepielewska, M.S.; MTPA) Poster Session: 4:00 p.m. - 6:00 p.m. ET, Wednesday, October 23 Smartphone Application-Mediated Supervised At-Home Telespirometry Erect and Supine Slow Vital Capacity (eSVC/sSVC) Measurements in Subjects With Amyotrophic Lateral Sclerosis Identify Statistically Significant Differences in eSVC/sSVC Decline as Function of Non-Invasive Ventilation Treatment Status [NCT05106569] (Eufrosina I. Young, M.D.; SUNY Upstate Medical University) Poster Session: 4:30 p.m. - 6:30 p.m. ET, Tuesday, October 22 Smartphone Application–Mediated, Supervised, At-Home Telespirometry Vital Capacity Measurements in Amyotrophic Lateral Sclerosis: Comparison of American Thoracic Society/European Respiratory Society Point-of-Care Quality Assessment Algorithms Implemented for Slow Vital Capacity and Forced Vital Capacity [NCT05106569] (Eufrosina I. Young, M.D.; SUNY Upstate Medical University) Poster Session: 4:30 p.m. - 6:30 p.m. ET, Tuesday, October 22 Compliance of Home-based Remote Digital Monitoring to Assess ALS progression (Track-ALS) (Katie Terrebonne; Emory University) Poster Session: 4:30 p.m. - 6:30 p.m. ET, Tuesday, October 22 Preclinical Data: Two preclinical studies will be presented, showcasing the effects of edaravone. The first study examines its impact on spinal motor neurons derived from induced pluripotent stem cells (iPSC) taken from a person with ALS carrying the A382T mutation in TDP-43. The second study investigates the role of edaravone on the modulation of glutamate-mediated hyperexcitability in spinal motor neurons using an ALS animal model. Transcriptomic Signature Induced by Edaravone in Motor Neurons From an ALS Patient With a TDP-43 Mutation (Satsuki Mikuriya, M.S.; MTPA) Poster Session: 4:00 p.m. - 6:00 p.m. ET, Wednesday, October 23 Edaravone Reduces the Enhanced Glutamatergic Transmission Onto Motor Neurons in the Spinal Cord of a Mouse Model of Amyotrophic Lateral Sclerosis (Alejandro Salah, M.D., Ph.D., MBA, MHA; MTPA) Poster Session: 4:00 p.m. - 6:00 p.m. ET, Wednesday, October 23 About RADICAVA® (edaravone) and RADICAVA ORS® (edaravone) The U.S. Food and Drug Administration (FDA) approved RADICAVA® (edaravone) on May 5, 2017, and the oral formulation RADICAVA ORS ® (edaravone) on May 12, 2022, for the treatment of amyotrophic lateral sclerosis (ALS). In 2024, the FDA recognized RADICAVA ORS with Orphan Drug Exclusivity based on the major contribution to patient care of the innovative oral formulation. RADICAVA is administered in 28-day cycles by intravenous (IV) infusion. It takes 60 minutes to receive each 60 mg dose. For the initial cycle, the treatment is infused daily for 14 consecutive days, followed by a two-week drug-free period. All cycles thereafter are infused daily for 10 days within a 14-day period, followed by a two-week drug-free period. RADICAVA ORS is taken daily for 14 consecutive days followed by a 14-day drug-free period for the initial treatment cycle. For subsequent treatment cycles, RADICAVA ORS is taken for 10 days within a 14-day period followed by a 14-day drug-free period. RADICAVA ORS should be taken in the morning after overnight fasting. Patients should not eat or drink (except water) within one hour after taking RADICAVA ORS.1 Edaravone was discovered and developed for ALS by Mitsubishi Tanabe Pharma Corporation (MTPC) and commercialized in the U.S. by Mitsubishi Tanabe Pharma America, Inc. (MTPA). The MTPC group companies began researching ALS in 2001 through an iterative clinical platform over a 13-year period. In 2015, edaravone was approved as RADICUT® for the treatment of ALS in Japan and South Korea. Marketing authorizations were subsequently granted in Canada (October 2018), Switzerland (January 2019), Indonesia (July 2020), Thailand (April 2021), Malaysia (December 2021) and Brazil (February 2024). Marketing authorization for RADICAVA® Oral Suspension was granted in Canada (November 2022) and Switzerland (May 2023), and RADICUT® Oral Suspension 2.1% was granted regulatory approval in Japan in December 2022. To date, in the U.S., RADICAVA and RADICAVA ORS have been used to treat over 16,000 people with ALS, with over 2.0-million days of therapy, and have been prescribed by over 2,400 HCPs.2-4 IMPORTANT SAFETY INFORMATION Hypersensitivity Reactions RADICAVA (edaravone) and RADICAVA ORS (edaravone) are contraindicated in patients with a history of hypersensitivity to edaravone or any of the inactive ingredients of this product. Hypersensitivity reactions (redness, wheals, and erythema multiforme) and cases of anaphylaxis (urticaria, decreased blood pressure, and dyspnea) have occurred with RADICAVA. Patients should be monitored carefully for hypersensitivity reactions. If hypersensitivity reactions occur, discontinue RADICAVA or RADICAVA ORS, treat per standard of care, and monitor until the condition resolves. Sulfite Allergic Reactions RADICAVA and RADICAVA ORS contain sodium bisulfite, a sulfite that may cause allergic-type reactions, including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in susceptible people. The overall prevalence of sulfite sensitivity in the general population is unknown but occurs more frequently in asthmatic people. Adverse Reactions The most common adverse reactions (≥10%) reported in RADICAVA-treated patients were contusion (15%), gait disturbance (13%), and headache (10%). In an open label study, fatigue was also observed in 7.6% of patients receiving RADICAVA ORS. Pregnancy Based on animal data, RADICAVA and RADICAVA ORS may cause fetal harm. To report suspected adverse reactions or product complaints, contact Mitsubishi Tanabe Pharma America, Inc., at 1-888-292-0058. You may also report suspected adverse reactions to the FDA at 1-800-FDA-1088 or . INDICATION RADICAVA and RADICAVA ORS are indicated for the treatment of amyotrophic lateral sclerosis (ALS). For more information, including full Prescribing Information, please visit . About Mitsubishi Tanabe Pharma America, Inc. Based in Jersey City, N.J., Mitsubishi Tanabe Pharma America, Inc. (MTPA) is a wholly-owned subsidiary of Mitsubishi Tanabe Pharma Corporation (MTPC). It was established by MTPC to develop and advance our pipeline as well as commercialize approved pharmaceutical products in North America. For more information, please visit or follow us on X (formerly Twitter), Facebook and LinkedIn. About Mitsubishi Tanabe Pharma Corporation Mitsubishi Tanabe Pharma Corporation (MTPC), the pharma arm of Mitsubishi Chemical Group (MCG), is one of the oldest pharmaceutical companies in the world, founded in 1678. MTPC is headquartered in Doshomachi, Osaka, the birthplace of Japan's pharmaceutical industry. MCG has positioned health care as its strategic focus in its management policy, "Forging the future". MTPC sets the MISSION of "Creating hope for all facing illness". To that end, MTPC is working on the disease areas of central nervous system, immuno-inflammation, diabetes and kidney, and cancer. MTPC is focusing on "precision medicine" to provide drugs with high treatment satisfaction and additionally working to develop "around the pill solutions" to address specific patient concerns based on therapeutic medicine, including prevention of diseases, pre-symptomatic disease care, prevention of aggravation and prognosis. For more information, go to . Media inquiries: [email protected] 1 RADICAVA and RADICAVA ORS Prescribing Information. Jersey City, NJ: Mitsubishi Tanabe Pharma America, Inc.; 2022. 2 Data on file. Mitsubishi Tanabe Pharma America, Inc. 3 Data on file. Mitsubishi Tanabe Pharma America, Inc. 4 Data on file. Mitsubishi Tanabe Pharma America, Inc. SOURCE Mitsubishi Tanabe Pharma America WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Results Presented in an Oral Presentation at the Society for Neuroscience Annual Meeting RNS60 Protected Motor Neurons and Neuromuscular Junctions and Reduced Neuroinflammation TACOMA, Wash., Oct. 9, 2024 /PRNewswire/ -- Revalesio, a clinical-stage pharmaceutical company developing treatments for acute and chronic neurological disorders, today announced new data showing that Revalesio's investigational therapeutic, RNS60, protected motor neurons in the prpTDP-43A315T-UeGFP mouse model of ALS. PrpTDP-43A315T-UeGFP mice express a mutation of the human TDP43 gene and develop progressive motor neuron degeneration, leading to gait abnormalities, muscle weakness, and eventually death, mimicking key features of ALS. TDP43-associated pathology is found in approximately 97% of people with ALS. The results were presented today during the Nanosymposium ALS Therapeutics at the Society for Neuroscience Annual Meeting. "There is a great need for treatment options to slow the progression of ALS," said Hande Ozdinler, Ph.D., Associate Professor of Neurology at Northwestern University Feinberg School of Medicine and Principal Investigator of the study. "These promising preclinical findings warrant further investigation of the potential role of RNS60 in protecting motor neurons and preserving mitochondrial function, key factors in the pathogenesis of ALS." "These exciting results suggest that RNS60 has potential to mitigate neurodegeneration due to TDP-43 pathology," said Mukesh Gautam, PhD, Research Assistant Professor of Neurology at Northwestern University Feinberg School of Medicine and presenting author at the Society for Neuroscience Annual Meeting. "Since TDP-43 pathology contributes to a large population of both familial and sporadic ALS patients, these results are particularly promising." In this study, 30-day old prpTDP-43A315T-UeGFP mice showing signs of degeneration were treated with RNS60 every other day for 60 days. Immunohistochemistry was performed to quantitatively assess activated microglia (immune cells that patrol the central nervous system [CNS] for pathogens and damage) and activated astrocytes (cells in the CNS that perform metabolic, structural, homeostatic, and neuroprotective tasks). Ultrastructural integrity of neuronal mitochondria was studied via electron microscopy. RNS60 treatment significantly a) improved mitochondrial ultrastructure in the motor neurons, b) reduced the extent of astrogliosis and microgliosis in mice and c) protected health and stability of upper motor neurons and neuromuscular junctions compared to placebo-treated mice. "These results add to the growing body of preclinical and clinical evidence that RNS60 may provide neuroprotective effects in ALS," said Bert van den Bergh, Revalesio's Executive Chairman on the Board of Directors, and former President of Neuroscience Products at Eli Lilly and Company. "We are simultaneously advancing RNS60 in planned clinical trials for the treatment of patients with ALS and ischemic stroke with the goal of improving the lives of people with these devastating conditions." About RNS60 RNS60 is an investigational therapeutic being developed to provide disease modifying and potentially restorative treatments for neurological diseases. In preclinical studies, RNS60 activated intracellular signaling pathways to increase mitochondrial biogenesis and function and reduce inflammation. RNS60 safely protected neurons and oligodendrocytes and modulated the activity of immune cells to restore homeostasis. RNS60 has been granted Orphan Drug and Fast Track designations for ALS from the U.S. Food and Drug Administration. About Revalesio Revalesio is a clinical-stage pharmaceutical company with a vision to change the future of treatment for acute and chronic neurological disorders. The company's lead clinical program for RNS60 is ischemic stroke with additional programs in ALS and other neurological disorders. The company's pioneering technology, founded in physics, addresses fundamental mechanisms involved with proper cellular function to slow disease progression and improve quality of life. For more information, please visit revalesio.com and engage with us on LinkedIn. Media Lori Murray [email protected] SOURCE Revalesio Corporation WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Researchers from the Francis Crick Institute and the UCL Queen Square Institute of Neurology have found a way to selectively target cells affected by motor neurone disease (MND). Published in the journal Science , the study details how the team developed DNA molecules that contain ‘invisibility cloak’ sequences, which can only be removed by diseased cells. It is hoped that preventing healthy cells from reading the molecules’ messages could lead to safer and more effective gene therapies for MND, as well as other neurodegenerative diseases, including frontotemporal dementia. “While neurodegenerative diseases have devastating effects, we can estimate that less than 0.00001% of cells in a patient’s body are actually diseased,” explained study lead Oscar Wilkins. “The challenge is finding a way to specifically target treatments to this minuscule fraction of diseased cells, while avoiding unnecessary treatment of the 99.99999% of cells which are healthy,” he said. Affecting up to 5,000 adults in the UK at any one time, MND is a rare condition that progressively damages parts of the nervous system and leads to muscle weakness, often with visible wasting. The team’s new approach centres around the activity of the TDP-43 protein, which resides near the DNA in healthy cells and helps them to correctly interpret the DNA’s genetic instructions. However, this protein gets stuck in distant parts of diseased cells, corrupting their interpretation of genetic messages. Using artificial intelligence prediction tools and careful design, the researchers created DNA sequences that behave in the opposite way – the messages from the DNA are corrupted in healthy cells, but can be interpreted correctly in diseased ones. Pietro Fratta, head of the molecular neurodegeneration laboratory at the Crick and UCL, who co-invented the approach, said: “We hope this new technology will enable much bolder therapeutic approaches for MND. “Many potential therapies also alter important cellular processes and this may cause toxicity. Therefore, limiting their action to diseased cells, while leaving healthy cells untouched, will increase the safety of gene therapies and allow researchers to pursue many more treatment options.” US collaborators from the National Institutes of Health’s Eunice Kennedy Shriver National Institute of Child Health and Human Development also contributed to the therapeutic approach. Work to further develop gene therapies for amyotrophic lateral sclerosis, the most common form of MND, using the system is being supported by the Crick Translation Fund and by the UCL Neurogenetics Therapy Programme.